Alpha-enolase (ENO1) is a multifunctional protein best known for its canonical role in glycolysis, but growing evidence indicates that it also plays important roles in cancer development and progression. This review summarizes the current knowledge regarding the biological and clinical significance of ENO1 across multiple cancer types. We first outline the physiological characteristics of ENO1 and its distribution in normal tissues. Then, we discuss its aberrant expression patterns and genomic alterations in human cancers. We further examine the evidence linking ENO1 to major cancer-related processes, including proliferation, apoptosis resistance, cancer stemness, autophagy, metastasis, drug resistance, and angiogenesis. In addition, we review studies that evaluate the association between ENO1 expression and patient prognosis in pan-cancer datasets and individual malignancies. Collectively, the available literature indicates that ENO1 is closely associated with malignant progression through its involvement in metabolic reprogramming and broader tumor-promoting cellular functions. These findings suggest that ENO1 may serve as a context-dependent biomarker and a candidate therapeutic target in selected cancer settings; however, further mechanistic validation and clinically annotated studies are required before its translational value can be firmly established.
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